As much as 68% to 77% of the population is estimated to have suboptimal (<30 ng/mL) levels of vitamin D.1,2 This important nutrient promotes skeletal health by enhancing the intestinal absorption of calcium and phosphorus. Deficiency is associated with bone diseases such as rickets, osteomalacia, and osteoporosis. Emerging evidence also suggests links to nonskeletal illnesses such as cancer (especially colorectal and breast), cardiovascular disease, and infectious and autoimmune diseases.3,4 Vitamin D toxicity, which manifests as hypercalcemia, hypercalciuria, or kidney stones, is rare but can result at serum levels above 150 ng/mL.4 Current guidelines recommend maintaining adequate vitamin D levels (with vitamin D supplementation if necessary) to maximize bone health and prevent bone disease.4-6 Accurate determination of vitamin D levels can help diagnose vitamin D deficiency and toxicity, and inform clinical management.

The term "vitamin D" typically refers to 2 molecular forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). Vitamin D3 is the main form and is produced in the skin in response to sunlight.4 However, both forms can be obtained in relatively small amounts through normal diet. Both are also available as over-the-counter supplements and as high-dose prescription formulations in the United States.3 Vitamin D3 is also available as a high-dose supplement.

Vitamins D2 and D3 are metabolized to produce different 25-hydroxyvitamin D (25[OH]D) forms: 25(OH)D2 and 25(OH)D3; these metabolites are then converted to their corresponding active forms.4 The sum of 25(OH)D2 and 25(OH)D3 concentrations yields the total 25(OH)D level, which is the accepted standard for determining vitamin D status.4 The active metabolite of vitamin D (1,25-dihydroxyvitamin D) is not useful for assessing vitamin D status because its levels are often normal or even elevated in patients with vitamin D deficiency.4

Quest Diagnostics offers the Vitamin D, 25-Hydroxy, Total, Immunoassay test (test code: 17306), which uses a chemiluminescent method to assess 25(OH)D status in serum. The method is standardized to the National Institute of Standards and Technology (NIST) standard reference material (SRM) 972, ensuring its accuracy. Furthermore, the test has also been certified by the Centers for Disease Control and Prevention (CDC) Vitamin D Standardization Certification Program, demonstrating precision and lack of bias in the method as compared to the CDC's LC/MS/MS reference method.

Individuals at increased risk for vitamin D deficiency (eg, pregnant, lactating, dark-skinned, elderly, obese, or housebound; those dwelling in latitudes higher than 33° north or 33° south; and infants who are breastfeeding without vitamin D supplementation or from vitamin D-deficient mothers)

Analytical specificity: 100% cross-reactivity with 25(OH)D2 and 25(OH)D3; 1.9% cross-reactivity with vitamin D2 and D3; 6.7% and 9.3% cross-reactivity with 1,25-dihydroxyvitamin D2 and D3, respectively; and 1.3% cross-reactivity with 3-epi-25(OH)D3

Reportable range: 4-150 ng/mL

For the LC/MS/MS method, use test code 92888 (children and adults) or 91935 (infants <3 years).

Interpretive Information

Abnormal 25(OH)D levels are associated with a range of conditions and medications (Table).3,4,7-16 There is no consensus about the optimal total 25(OH)D level, which may vary with the assay used and functional outcome measured. However, many experts accept a minimum of 30 ng/mL with a range of 40 to 60 ng/mL as optimal.3 A level up to 100 ng/mL is considered to be safe.3,4 Total 25(OH)D levels ≤20 ng/mL suggest vitamin D deficiency, while levels between 21 and 29 ng/mL suggest insufficiency.4 Expert opinions also vary about what constitutes 25(OH)D toxicity, with reported thresholds ranging from 50 ng/mL for outcome measures such as increased risk for mortality not related to calcium and bone metabolism (125 nmol/L)1 to 150 ng/mL (374 nmol/L) for mortality related to calcium and bone metabolism.

Table. Effect of Various Disorders and Medications on 25-Hydroxyvitamin D Concentration3,4,7-16